"Effects of chronic and acute cocaine treatment on the onset of maternal behavior and aggression in Sprague-Dawley rats": Correction.

Reports an error in the original article by J. M. Johns et al (Behavioral Neuroscience, 1994[Feb], Vol 108[1], 107–212). On page 108, in the Results, Maternal Behavior, the phrase in parentheses, "(8 min to crouch for 8 min or more of 30 min)' should read: "(6 min to crouch for 8 min or more of 30 min).' On page 109, the label on the upper right panel of Figure 1, "Percent That Crouch in 8 Minutes,' should read: "Percent That Crouch in 6 Minutes.' (The following abstract of this article originally appeared in record 1994-24731-001.) Pregnant rats (N?=?17) were treated either throughout gestation (Gestational Day 1–20) with 30 mg/kg per day (chronic cocaine) or with 1 15-mg/kg dose immediately following parturition (acute cocaine). Chronic and acute cocaine treatment delayed or diminished the postpartum onset of some components of maternal behavior, and chronically treated dams were significantly more aggressive toward a male intruder than acute cocaine-treated or saline-treated dams. Cocaine increased the latency to crouch over pups and decreased crouch duration during a 30-min observation period that immediately followed parturition. Latencies to nest build were also longer in more chronic cocaine-treated dams than in saline controls.… (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Time course of postpartum aggression in rats (Rattus norvegicus).

The time course of postpartum aggression was examined in primiparous Long-Evans rats (N?=?77). Individually housed lactating females (n?=?7 per condition) were randomly assigned to 1 of 11 conditions (day of testing), with each subject tested once between Day 0 (the day of parturition) through Day 20 postpartum. Duration of aggression was highest and latency to attack was shortest on Day 0, with all dams attacking an unfamiliar intruding male during 10-min tests. The proportion of dams engaging in attack remained high through the end of the first week of lactation, but decreased sharply during the third week postpartum. The findings indicate that the probability and intensity of maternal aggression is closely associated with the time since parturition at which tests are given. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparison of two positive reinforcing stimuli: Pups and cocaine throughout the postpartum period.

This set of experiments investigated the appetitive or motivational processes underlying the performance of maternal behavior. The place preference paradigm was adapted to simultaneously investigate the reinforcing properties of cocaine and pups for maternal, lactating dams. These modifications allowed the authors to assess which stimulus, either a 10 mg/kg sc injection of cocaine or 3 pups, had the strongest reinforcing value. At Postpartum Days 10 and 16, the dams preferred the cocaine cue-associated chamber, whereas the dams tested at Postpartum Day 8 preferred the pup cue-associated chamber. Overall, the data revealed an interaction between the postpartum period at testing and the exhibited preference for cocaine or pups. Further testing will investigate the neural circuitry underlying the appetitive processes of each stimulus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Experiential determinants of postpartum aggression in mice.

Explored the experiential determinants and the social controls of postpartum aggression in inbred ICR mice. In Exp I, 7 lactating females were tested repeatedly from Day 2 to Day 22 postpartum against male mice; attacks by the females continued through Day 18. Two other groups of 7 females tested only once showed diminished attacks against males by Day 14 postpartum. In Exp II, 8 females were paired with a male for 1 wk prior to parturition; they showed reliably fewer attacks on Day 2 postpartum than a group of 9 females that were isolated prior to parturition. All of these results were obtained in a standard 3-min test. A 24-hr test on Day 4 of Exp II revealed that in both groups female attacks dropped to near zero after 30 min. After female attacks declined, males initiated social behavior which occasioned vocalizations by the females. Further, males attacked in 65% of the tests and destroyed the litters of the females in 53% of the tests. The behavior of the male exerted important influences on the structure of extended female–male interactions. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prenatal exposure to cocaine: effects on aggression in Sprague-Dawley rats

Social/aggressive behavior in adult rat offspring (beginning at postnatal Day 180) prenatally exposed to saline, cocaine, or amfonelic acid (AFA) was examined. Pregnant rats received injections of 15 mg/kg of cocaine, or 0.9% saline twice daily, s.c., or on 2 consecutive days at 4-day intervals, or 1.5 mg/kg amfonelic acid daily throughout gestational Days 1-20. Frequency, duration, and latency of 11 social/aggressive behaviors were recorded for two 15-min sessions during which a smaller male intruder replaced an ovariectomized female in the resident's home cage. Subjects received a s.c. saline injection before Session 1 and 2.0 mg/kg of gepirone, a 5HT1a partial agonist, prior to Session 2. Prenatal cocaine treatment resulted in alterations of aggressive behavior. Aggressive behavior was reduced by gepirone in all groups but to a lesser extent in the AFA group.     

An oxytocin antagonist infused into the central nucleus of the amygdala increases maternal aggressive behavior.

Decreased oxytocin levels in the amygdalas of rat dams following chronic gestational cocaine exposure have been correlated with heightened maternal aggressive behavior. In this experiment, drug-naive dams were implanted with bilateral cannulas into the central nucleus of the amygdala (CNA) or control area and infused with 1,000 or 500 ng of an oxytocin antagonist (OTA) or buffer, 4 hr before testing. Behavior was compared among dams infused with OTA into target areas just outside the CNA and cocaine-treated dams (infused with buffer). Dams infused with 1,000 ng OTA attacked intruders significantly more often than buffer-infused dams. OTA did not affect other behaviors, suggesting that disruption of oxytocin activity in the CNA may be sufficient to selectively alter maternal aggressive behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cocaine sensitization can accelerate the onset of peak cocaine behavioral effects

The development of sensitization to the behavioral effects of cocaine occurs with repeated intermittent usage. In the present study rats were given five daily i.p. injections of cocaine (10 mg/kg) immediately prior to placement in an open-field environment for 20 min to induce cocaine sensitization. Control groups received saline injections or cocaine injections (10 mg/kg) 30 min after testing in the home cage. One week later the animals were given a challenge test with 10 mg/kg cocaine. The animals that had received cocaine in the test environment exhibited a more rapid onset of cocaine-induced behavioral effects than either animals previously treated with saline or animals that had received cocaine in the home cage. In a second experiment, the same sensitization protocol was followed except that during the interval between the end of the cocaine/saline treatments and the challenge test, the animals were given six daily 20-min saline tests to assess the contribution of differential habituation and/or Pavlovian conditioning to the sensitization effect. Neither habituation or Pavlovian conditioning altered the more rapid onset of cocaine stimulant effects induced by repeated cocaine treatments. It is suggested that the faster onset of cocaine effects is another way in which cocaine sensitization contributes to cocaine abuse liability.     

Involvement of dopamine D2 receptors in the effect of cocaine on sexual behaviour and stretching-yawning of male rats

The effect of cocaine (7.5, 15 and 30 mg/kg) administered in acute or subchronic mode, on the mating behaviour of sexually active male rats varied in a dose- and mode-dependent manner. Regardless of mode of treatment, 30 mg/kg markedly impaired the rats copulatory ability and impairment continued for a week after suspension of subchronic treatment. An acute dose of 15 mg/kg reduced intromission frequency, while in subchronic mode it also reduced ejaculation latency. Mount frequency was increased by 7.5 and 15 mg/kg, but only on first injection. In the case of sexually-naive male rats, acute administration of cocaine (3-30 mg/kg) stimulated penile erections at 7.5 mg/kg and motor hyperactivity at all doses. (-) Eticlopride (0.025 and 0.05 mg/kg), a DA D2 antagonist, counteracted cocaine-induced motor hyperactivity but not penile erection, which it enhanced. (-) Eticlopride at the same doses also antagonized cocaine potentiation of lisuride (0.2 mg/kg)-induced behavioural effects. When male rats treated with subchronic cocaine (15 mg/kg) were injected with the DA D2 agonist SND 919 (0.1 mg/kg), they displayed a more marked stretching-yawning behaviour than control animals receiving SND 919 at the same dose. The involvement of DA D2 receptors in cocaine-induced effects is suggested.     

cAMP-signaling pathway acts in selective synergism with glucose or tolbutamide to increase cytosolic Ca2+ in rat pancreatic beta-cells

The effect of repeated cocaine administration on serotonin2 (5-HT2) receptor function was examined in male rats. Rats were fitted with indwelling jugular catheters and subsequently received cocaine (15 mg/kg, i.p., b.i.d.) or saline for 7 days. Rats were challenged with the 5-HT2 agonist DOI (25, 100, 400 micrograms/kg, i.v.) or saline 42 hr and 8 days after cessation of chronic treatment. Serial blood samples were collected at various times after DOI challenge and analyzed for prolactin levels. DOI-induced head shakes and skin jerks were examined concurrently in the same subjects. After 42 hr of withdrawal, the stimulatory effects of DOI on prolactin release and shaking behavior were significantly enhanced in cocaine-treated rats. Conversely, the skin jerk response to DOI was not altered by prior cocaine exposure. After 8 days of withdrawal, the prolactin and head shake responses to DOI were still potentiated in cocaine-treated rats, but this effect was no longer statistically significant. The data indicate that chronic cocaine enhances the sensitivity of 5-HT2 receptor mechanisms. Our findings further suggest the possibility that altered 5-HT2 receptor function may be involved in the mood disturbances experienced by abstinent cocaine addicts.     

Effects of acute and delayed effects of prior chronic cocaine administration on regional rates of cerebral protein synthesis in rats

Single or repeated treatments with cocaine (15 mg/kg, i.p.) in rats modify rates of local cerebral protein synthesis (ICPSleu) measured with the [1-14C]leucine method. A single dose of cocaine to naive rats reduced ICPSleu by about 10% throughout the brain; the most statistically significant reduction was in the nucleus accumbens, shell portion (P = .0003). A comparable dose of cocaine administered acutely after 1 wk of daily cocaine injections had no effects on ICPSleu. Delayed effects of prior chronic cocaine treatment were studied in experiments in which one rat of each pair received injections with saline for 8 days and the other cocaine, and on the 15th day ICPSleu was measured. In these experiments delayed effects of the chronic cocaine treatment were observed; in the cocaine-treated rats ICPSleu was significantly increased in selective brain regions, i.e., prefrontal and primary olfactory cortex (P < .006). These results suggest that acute effects of a single dose of cocaine and residual effects of chronic cocaine treatment on ICPSleu are distinctly different and occur in different regions of the brain.     

Intravenous gestational cocaine in rats: effects on offspring development and weanling behavior

Pregnant rats were injected with cocaine (CN; 6 mg/kg) or an equal volume of saline (SAL), via the tail vein, on gestation days 8-20. A third group was untreated (UT). Maternal weight gain was not affected by dam treatment despite slight differences in food intake. Litter characteristics (e.g., litter size, pup weight) did not differ among groups. Indices of fetal mortality were not affected by the treatments. Developmental tests, initiated on postnatal day (PND) 2, indicated slight delays in the negative geotaxic response and eye opening in cocaine-exposed pups. Open-field and tail-flick tests were performed on PND 21. Pups were acutely injected with cocaine (10 mg/kg, IP), saline, or received no treatment before placement in a novel open field; morphine (1.5 mg/kg, SC) or saline was injected prior to the tail flick test. Pups from CN dams exhibited a significant decrease in spontaneous exploratory behavior compared to both controls, and a time-dependent increase in rearing compared to pups from UT dams. The acute cocaine injection prior to placement in the open field did not alter locomotion or rearing among dam treatment groups. However, the acute cocaine injection did increase stereotypy ratings for female pups from CN dams compared to similarly treated males, and females from SAL and UT dams. No differences were observed among groups in the tail-flick test. These data suggest that the IV route of administration provides a viable method of cocaine delivery in pregnant rats, and provides further evidence of the developmental and behavioral teratogenicity of prenatal cocaine exposure.     

Human energy and work in a European village

In a mouse model of transplacental cocaine exposure we have demonstrated alterations in brain structure and function of offspring including disturbances of brain growth, disruption of neocortical cytoarchitecture, and transient as well as persistent behavioral deficits. One mechanism by which cocaine may alter fetal brain development is through cocaine-induced alpha-adrenergic-mediated (uterine) arterial vasoconstriction. In this study pregnant Swiss Webster (SW) mice were injected with cocaine HCl (20 or 40 mg/kg, SC) without any changes evident in mean arterial blood pressure (MAP) measurements. These physiology results suggest that in our mouse model, cocaine's transplacental effects on the fetus are not due to cocaine-induced maternal vasoconstriction, nor concomitant hypoperfusion of the fetus. In a separate series of experiments, pregnant SW dams were administered cocaine HCl at 40 mg/kg/day (COC 40), 20 mg/kg/day (COC 20), or 10 mg/kg/day (COC 10) [SC, divided in two daily doses, from embryonic day (E) 8 to E17 inclusive]. Additional groups of cocaine-treated dams were administered phentolamine (5 mg/kg, SC), a short-acting alpha-adrenergic antagonist, 15 min prior to each cocaine dose (Phent COC 40, Phent COC 20, Phent COC 10). Animals born to Phent COC 40 dams demonstrated transient postnatal brain growth retardation and behavioral deficits in first-order conditioning of P9 mice comparable to mice born to COC 40 dams, which received the same regimen of cocaine injections without phentolamine pretreatment. Like COC 40 offspring, Phent COC 40 offspring also demonstrated a persistent deficit in the blocking paradigm. The behavioral and growth findings confirm and extend the physiology data, and imply that in our rodent model, alpha-adrenergic mechanisms (including maternal vasoconstriction) are unlikely to mediate these toxic effects of transplacental cocaine exposure on developing brain.     

Alterations in locomotor activity during chronic cocaine administration: effect on dopamine receptors and interaction with opioids

Chronic cocaine administration can produce tolerance or sensitization to locomotor activating effects, depending on the treatment paradigm. The effects of chronic, continuous cocaine were measured on locomotor activity for 1 hr daily for 7 days. Cocaine produced significant increases in locomotor activity 4 hr after osmotic minipumps were implanted, and an even higher level of activity after 24 hr. This was likely a rapid sensitization to the locomotor activating effects of cocaine, because neither brain nor plasma levels of cocaine were significantly altered over the treatment period. By day 4, activity levels diminished, but remained significantly higher than in saline-treated animals. Twenty-four hr after pump removal, there were no changes in dopamine D1 or D2 receptor binding, or in dopamine-stimulation of adenylyl cyclase activity in either caudate putamen or nucleus accumbens of cocaine-treated animals. Chronic naltrexone produced a slight, nonsignificant decrease in locomotor activity and when combined with cocaine, produced the same pattern of activity as cocaine alone, but with slightly less stimulation on all days. Morphine produced a smaller increase in activity than cocaine that remained constant throughout the treatment week. Cocaine with morphine was additive, producing greater activity and less tolerance than cocaine alone. Thus, continuous cocaine administration produces a rapid sensitization that is lost over the course of the treatment period, yet does not produce any immediate alterations in dopamine receptors or regulation of adenylyl cyclase. The pattern of behavior is not altered by an opioid antagonist, while the sensitization period appears to be prolonged in the presence of an opioid agonist.     

Muscle metabolism of professional athletes using 31P-spectroscopy

PURPOSE: Cocaine abuse has reached epidemic proportions in the United States. Our recent study has shown that cocaine has adverse action on spermatogenesis and fertility in male rats. The indirect action of cocaine occurs by blocking the reuptake of neurotransmitter, which causes local vasoconstriction. In this study we evaluate blood flow to the testes after subcutaneous injection of cocaine to male rats. METHODS: Male Sprague-Dawley rats were divided into two main groups. The treatment group received subcutaneous cocaine (30 mg/kg body weight) and the control animals received normal saline. Xenon-133 wash out experiments were carried out on testes at 5, 10, 15, 20, 30, 45, 60, 90 min and 4.5 hours after injection of cocaine or normal saline. Statistical analysis was done by SPSS V. 7.S for windows. P < 0.05 was considered statistically significant. RESULTS: There was a reduction in testicular blood flow after cocaine administration to male rats. This vasoconstrictor effect was most pronounced at 15 min after injection of cocaine and persisted up to 60 min. At 90 min, the early restitution of blood flow to ischemic tissue occurred. There was a significant increase in testicular blood flow in cocaine-treated groups than in the control group during restitution phases at 90 min. At 4.5 hours, there was no difference in blood flow in both groups. CONCLUSION: This study demonstrates that cocaine, when given subcutaneously at a 30 mg/kg body weight dose, results in prolonged vasoconstriction of the blood vessels to the testes. Adverse effects of cocaine on the testes may be in part due to ischemic and postischemic reperfusion injury to the organ.     

Cocaine-induced effects on isolation stress in neonatal rats.

The effects of cocaine administration on isolation-induced vocalizations and activity levels in 10-day-old rat pups were examined. Day 10 pups given cocaine (1.25, 2.5, 5, 10, and 20 mg/kg ip) vocalized significantly less than their caffeine- (10 mg/kg) and saline-administered siblings during a 5-min isolation period. Cocaine- and caffeine-administered pups also demonstrated a significant increase in overall activity compared with controls. In addition, ip administration of the dopamine antagonist haloperidol (0.5 and 1.0 mg/kg) before 1.25 and 2.5 mg/kg cocaine produced a significant elevation in vocalizations compared with saline pretreatment, which indicates a blocking of cocaine's effect on calling behavior. These results suggest that the endogenous dopamine system involved with reinforcement and reward may quell the stress of isolation in the infant rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Plasma cocaine levels and locomotor activity after systemic injection in virgin and in lactating maternal female rats

We have determined the temporal pattern of plasma cocaine levels and increased activity that result from acute systemic injections of cocaine to female rats in two different endocrine and behavioral states, in nonmaternal virgins and in lactating maternal dams. Plasma levels of cocaine as well as ambulatory and rearing activity were determined every 30 min for a total of 300 min after subcutaneous injections of either 10, 20, or 40 mg/kg of cocaine. Virgin females had no prior drug history, whereas lactating, maternal dams had received two cocaine injections before activity testing. Within 30 min after an injection, cocaine in the plasma and activity were substantially elevated, and generally remained so for 270-300 min. Overall, plasma cocaine levels and activity were well correlated and followed a predictable dose-response pattern. The onset, peak, duration, and decline of activity corresponded generally to the onset, peak, duration, and decline of plasma cocaine. For virgins, mean ambulatory activity increased 2.5-4.0-fold over baseline, whereas in lactating females activity increased 5-11-fold over baseline. Stereotypy did not occur. Although the general responsivity of these females to cocaine was very similar to that reported for males, there are differences in the timing of peak activity and the return of activity to baseline when the virgins and the lactating dams are compared to each other and to reports by others on male rats. These data support the hypothesis that endocrine or behavioral state may influence the responsiveness of animals to cocaine.     

Prostaglandin F2alpha-induced luteolysis of aging corpora lutea in hysterectomized pigs

Prostaglandins primarily of uterine origin play an important role in parturition. Hysterectomy of nongravid pigs early in the luteal phase maintains luteal function until about Day 150, whereas the duration of normal pregnancy is about 114 days. A precisely timed peak release of relaxin and coincident decrease in progesterone secretion in unmated hysterectomized gilts are similar to hormonal changes that occur a few hours before parturition. It is hypothesized that prostaglandin F2alpha (PGF2alpha) in hysterectomized pigs mimics abrupt changes in ovarian and pituitary hormone secretion seen before normal parturition and in early lactation. Unmated Yorkshire gilts were hysterectomized on Days 6-8 of a normal estrous cycle, and at 1200 h on Day 113, they were given an i.m. injection of 30 mg PGF2alpha-trihydroxymethylaminomethane (THAM) salt or PBS. None of these gilts expressed behavioral estrus immediately after PGF2alpha or vehicle treatment. On Day 113, PGF2alpha increased peak relaxin (60 ng/ml) compared with that of controls (34 ng/ml; p < 0.01), whereas progesterone decreased abruptly (4 vs. 16 ng/ml in PGF2alpha and PBS; p < 0.01). Prolactin remained at < 5 ng/ml from Day 98 to 120 in controls but peaked at 33 ng/ml immediately after PGF2alpha treatment on Day 113, and then decreased to levels similar to those of controls on Day 120. Sequential bleeding revealed an acute growth hormone release (4.5 ng/ml) immediately after PGF2alpha injection and return to basal levels (< 0.6 ng/ml) on Days 114-120. PGF2alpha induced abrupt shifts in progesterone, relaxin, prolactin, and growth hormone secretion in hysterectomized gilts that mimicked hormone changes seen in late pregnancy, parturition, and early lactation. These findings provide new insight into the role of PGF2alpha in abruptly changing hormone secretions by aging corpora lutea and the pituitary gland even in the absence of conceptuses or the uterus in the pig.     

Changes in dopamine, serotonin and their metabolites in discrete brain areas of rat offspring after in utero exposure to cocaine or related drugs

The concentrations of dopamine (DA), serotonin (5HT) and their metabolites were quantified in 5 brain areas of rats exposed to saline, cocaine (15 mg/kg b.i.d.), amitriptyline (10 mg/kg), or amfonelic acid (AFA, 1.5 mg/kg) throughout gestation. Male pups from 3 similarly treated dams were fostered to 2 surrogate dams. The process of breeding and rearing was repeated 4 times with new dams to build the groups to 4-12, since only one pup per litter was used for any one measurement. AFA was used to mimic the dopamine (DA) uptake blockade and stimulant properties of cocaine and amitriptyline was used to mimic the other pharmacological effects of cocaine. At postnatal days (PND) 30, 60, and 180, one pup per litter was removed for HPLC analysis of monoamines. A second pup received 0.3 mg/kg haloperidol, catalepsy assessed after 1 hr, and the brain used for analysis. The cataleptic response to haloperidol was unaffected by any prenatal treatment. The striatum from PND 30 cocaine rats had decreased levels of DA without a decrease in DA metabolites. At PND 60 in cocaine exposed rats, DA and DOPAC concentrations were increased, and 5HT levels were decreased in the striatum. The amitriptyline-exposed group exhibited decreased 5HT and 5-HIAA levels in the striatum. The hypothalamus of the cocaine group had lower levels of 5-HIAA, and other brain areas had a trend for lower levels of 5HT and 5-HIAA. At PND 180, DOPAC was increased in the striatum and prefrontal cortex of the cocaine group. Haloperidol-induced altered monoamine metabolism was unaffected by any prenatal treatment at any age. These data suggest that age-related changes in the DA and 5HT neurotransmission systems occur in rats exposed prenatally to cocaine. However, the ability of the dopaminergic system to respond to a challenge by a DA receptor blocker is unaltered by these in utero treatments.     

Effects of cocaine administration during early organogenesis on prenatal development and postnatal growth in mice

Cocaine use has been associated with adverse developmental effects in humans. However, clinical reports both confirm and deny an association between cocaine use and malformations. Similarly, differences in species and strain, as well as route and timing of cocaine administration, have added to the difficulties in determining the teratogenicity of cocaine in animal models. This study was undertaken to compare the effects of dose, route, and timing of cocaine administration in ICR mice during early organogenesis. A single intraperitoneal (ip) administration of cocaine ( > or = 60 mg/kg) on Day 9 of gestation (plug day = 1) produced maternal lethality. The predominant developmental effect of cocaine administration was an increase in the percentage of litters exhibiting an enlarged renal pelvis. Despite a high incidence of affected pups at these doses, the enlargement was not severe. These results, in agreement with previous reports, provide further evidence that the developing urogenital system is sensitive to cocaine administration. When cocaine was administered using a subcutaneous route, pup weights were greater and the incidence of enlarged renal pelvis was lower than when an ip route was used. To better mimic human binge cocaine abuse, the toxicity of a "split dose" was determined. A 60 mg/kg dose was administered using one administration of 60 mg/kg, two treatments of 30 mg/kg, or three administrations of 20 mg/kg with 1 hr separating the treatments. The incidence of enlarged renal pelvis was similar when cocaine was administered as one or two but was decreased when cocaine was administered as three treatments. Both the route and split-dose studies suggest that high-peak serum concentrations are required to perturb development. There were no differences in the incidence or severity of enlarged renal pelvis when cocaine was administered on Day 8, 9, or 10 or on all 3 days of gestation. This suggested that the increase in enlarged renal pelvis may not be a specific teratogenic effect of cocaine administration but may be a delay of normal development induced by cocaine exposure during this early period of organogenesis. To address this hypothesis, cocaine was administered on Day 9 using an ip route and the pups were allowed to be naturally born. In pups whose mothers received cocaine there was an increase in postnatal deaths and a trend toward a reduction in pup body weight/litter at Postnatal Day 21. However, when renal morphology was assessed on Postnatal Day 21 no abnormal kidneys were seen. This supports the hypothesis that enlarged renal pelvis produced by cocaine administration during early organogenesis represents a developmental delay and not a persistent teratogenic defect. These studies suggest that high peak cocaine concentrations are required to delay normal kidney morphogenesis in mice.     

Anisomycin disrupts a contextual memory following reactivation in a cocaine-induced locomotor activity paradigm.

In experiments examining the potential reconsolidation of drug-associated contextual memories, rats were given a single pairing of cocaine with a specific context, and the ability of the protein synthesis inhibitor anisomycin administered following a context-only memory retrieval trial to impair conditioned locomotor sensitization was tested. Rats receiving 150 mg/kg anisomycin immediately following a 5-min reexposure to the cocaine-conditioned context showed decreased activity compared with the vehicle control group in response to a low-dose cocaine challenge during a subsequent test for conditioned sensitization. This effect was not seen when anisomycin was administered following a 30-min reexposure to the context or when anisomycin was administered 25 min after a 5-min reexposure. These results are consistent with a growing literature suggesting that following retrieval, associative contextual memories may undergo a transient protein synthesis-dependent reconsolidation phase that normally serves to maintain memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)